Impact of Opiate–HIV-1 Interactions on Neurotoxic Signaling
| Autor: | Annadora J. Bruce-Keller, Pamela E. Knapp, Kurt F. Hauser, William R. Tyor, Nazira El-Hage, Avindra Nath, Shreya Buch |
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| Rok vydání: | 2006 |
| Předmět: |
Narcotics
AIDS Dementia Complex p38 mitogen-activated protein kinases Immunology Neuroscience (miscellaneous) Biology Proinflammatory cytokine medicine Animals Humans Immunology and Allergy Protein kinase B Neurons Pharmacology Microglia Kinase Neurotoxicity Brain Opioid-Related Disorders medicine.disease medicine.anatomical_structure Neuroimmunology nervous system HIV-1 Opiate Neuroglia Neuroscience |
| Zdroj: | Journal of Neuroimmune Pharmacology. 1:98-105 |
| ISSN: | 1557-1904 1557-1890 |
| DOI: | 10.1007/s11481-005-9000-4 |
| Popis: | Opiate drug abuse exacerbates the pathogenesis of human immunodeficiency virus-1 (HIV-1) in the central nervous system through direct actions on glia and neurons. Opiate abuse causes widespread disruption of astroglial and microglial function, and significant increases in astroglial-derived proinflammatory cytokines and chemokines, which likely contributes to neuronal dysfunction, death, and HIV encephalitis. Neurons are also directly affected by opiate-HIV-1 interactions. HIV-1 and the viral proteins gp120 and Tat activate multiple caspase-dependent and caspase-independent proapoptotic pathways in neurons involving phosphatidylinositol 3-kinase (PI3 kinase)/Akt, as well as p38, c-Jun N-terminal kinase (JNK) and/or other mitogen-activated protein kinases (MAPKs). Opiates appear to decrease the threshold for HIV-1-mediated neurotoxicity by sending convergent signals that exacerbate proapoptotic events induced by viral and cellular toxic products. The synergistic proinflammatory and neurotoxic effects of opiate drugs on glia and neurons are largely mediated through mu opioid receptors, which are expressed by subpopulations of astroglia, microglia, and neurons. Opiate abuse intrinsically modifies the host response to HIV-1. Identification of how this occurs is providing considerable insight toward understanding the mechanisms underlying HIV-1-associated dementia. |
| Databáze: | OpenAIRE |
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